The neuropathology/imaging core (Core D) is essential for the successful achievement of the aims of this program because all projects rely upon morphological methods. Since many of the core services are specialized, it would not be efficient or economical for individual project leaders to support the required equipment and expertise in their own laboratories. Core D will provide service, expertise, and equipment for the detection of huntingtin, apolipoprotein E and its fragments, alpha-synuclein, and amyloid beta peptides in cells and tissues, and for the morphological characterization of the neural alterations these molecules elicit. Specifically, Core D will provide advice on and assistance in specimen processing, embedding and microtomy of paraffin wax-embedded and frozen tissues, vibratome sectioning, histochemistry, immunohistochemistry, immunocytochemistry, in situ hybridization, quantitative morphometry of histological sections, quantitation of neuritic branching, stereological cell counting, digital photomicrography, image analysis, fluorescence confocal microscopy, video microscopy and routine and specialized electron microscopy of thin-sectioned neural tissue samples, and immunogold cytochemistry. Core D will train project personnel in morphological techniques, establish standardized protocols, and provide assistance in the interpretation of imaging and neuropathological data. Core D will also keep track of tissue samples and slides by means of an on-line database. The core will operate under the co-leadership of Dr. David Sanan, a specialist in microscopy, and Dr. Eliezer Masliah, an expert in neuropathology. All the equipment and laboratory facilities necessary for performing Core D operations are available at the Gladstone Institutes in San Francisco and Dr. Masliah's laboratory at the University of California at San Diego. The five projects will make extensive use of the core throughout the five-year period.